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Optical Coherence Tomography and Neuro-Ophthalmology

Chen, John J., MD, PhD

Journal of Neuro-Ophthalmology: March 2018 - Volume 38 - Issue 1 - p e5–e8
doi: 10.1097/WNO.0000000000000505
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Department of Ophthalmology, Mayo Clinic Rochester, Rochester, Minnesota.

Address correspondence to John J. Chen, MD, PhD, Department of Ophthalmology, Mayo Clinic Rochester, Rochester, MN 55905; E-mail: chen.john@mayo.edu

Over the past decade, the Journal of Neuro-Ophthalmology has published approximately 70 articles pertaining to optical coherence tomography (OCT). In addition, OCT is used in almost every article describing an optic neuropathy since 2006 and, therefore, there are a countless number of articles that mention OCT. This is an amazing amount of literature considering that OCT has only been commercially available since 2002. Various versions of OCT machines are now found in almost every ophthalmology and neuro-ophthalmology clinic and have become essential in facilitating the ability to diagnose and monitor many retinal and optic nerve disorders.

The initial OCT machines used time-domain technology and had lower resolution, but still allowed for measurement of the peripapillary retinal nerve fiber layer (RNFL) (1). This led to improved detection of optic neuropathies, including glaucoma and nonglaucomatous optic neuropathies. The technology of OCT has been continuously improving, resulting in faster scans, better resolution, and improved analysis of the data, which were discussed in several reviews (2–4). These advances have led to the ability to segment and measure the thickness of the macular ganglion cell-inner plexiform layers, which has many applications in neuro-ophthalmology that were detailed by both Kardon and Lam (5,6). A recent study reported the use of multicolor imaging to view various layers of the retina and optic nerve (7).

OCT is very useful in the setting of papilledema, which was reviewed in an article by Kardon (8), “Optical coherence tomography in papilledema: what am I missing?” OCT can be used to measure the RNFL thickness and quantify the amount of optic disc edema. In addition, analysis of the macula and the ganglion cell layer allows for the ability to detect and monitor optic neuropathy in the presence of disc edema. A recent article reported thinning of the macula in the setting of resolving papilledema, especially in patients with atrophic papilledema (9). Two separate studies showed that retinal ganglion cell layer loss precedes RNFL thinning in optic neuritis (10) and nonarteritic anterior ischemic optic neuropathy (11).

The orientation of Bruch membrane and the retinal pigment epithelium (RPE) has been shown to be helpful in differentiating papilledema for other optic neuropathies. With raised intracranial pressure, there is an upward deflection of peripapillary RPE and Bruch membrane on OCT, which normalizes when papilledema resolves (12,13). Sibony et al (14) found that the peripapillary RPE also has an upward deflection toward the vitreous in patients with optic nerve sheath meningioma. By contrast, a backward deflection of the lamina cribrosa from low intracranial pressure may be detected in normal tension glaucoma (15).

OCT is critical in providing insight into the structural causes for glaucoma and differentiating glaucoma from nonglaucomatous optic neuropathy (16,17). In addition to changes in the lamina cribrosa orientation, enhanced depth-OCT has demonstrated that the lamina cribrosa tends to be thinner with more focal defects in normal tension glaucoma compared with high-pressure glaucoma (18,19).

OCT is helpful in diagnosing and monitoring optic disc drusen. A study using spectral-domain OCT showed that OCT was helpful in differentiating optic disc drusen from papilledema (20). Enhanced depth imaging and swept source OCT allow for deeper imaging and were shown to improve detection and imaging of optic nerve head drusen (21). A recent study showed that peripapillary RNFL thinning correlated with the anatomic location of optic disc drusen and visual field defects, especially in patients with superficial optic disc drusen (22).

OCT can be used to localize lesions along the visual pathway. Thinning of the macular ganglion cell layer is seen early in cases of toxic and nutritional optic neuropathy, which supports the concept that the papillomacular bundle is primarily damaged in this optic neuropathy (23). OCT also is helpful in detecting chiasmal injury. A case report discussed the use of OCT to identify the chiasmal hypoplasia variant of septo-optic dysplasia, causing thinning of the nasal and temporal quadrants of the peripapillary RNFL, in contrast to glaucoma that tends to affect the superior and inferior poles (24). Although the pattern of the RNFL thinning can sometimes detect chiasmal injury, a recent study evaluating chiasmal compression from tumors showed that analysis of the macular ganglion cell complex is more sensitive than measurement of the peripapillary RNFL (25). Chiasmal compression from tumor leads to a preferential thinning of the macular ganglion cell complex in the nasal hemiretina (8,26,27). Analysis of the macular ganglion cell complex also can help predict visual recovery following pituitary tumor surgery, where patients with less ganglion cell loss have better postoperative visual field results (25). While binasal thinning of the macular ganglion cell layer is seen in chiasmal injury, optic tract lesions cause homonymous hemimacular thinning, which was seen in a case report of optic tract injury from neuromyelitis optica (28).

In 2 studies, OCT demonstrated that isolated occipital lesions may cause transsynaptic retrograde retinal degeneration and homonymous ganglion cell complex thinning (29,30). In contrast to optic tract lesions, where thinning is seen within weeks of injury, transsynaptic retrograde degeneration likely takes many months or years to develop. The observation of transsynaptic retrograde degeneration has implications in using OCT in neurodegenerative conditions.

OCT has been proposed as a method of monitoring neurodegenerative diseases where the eye serves as the “window to the brain.” Iseri et al (31) showed RNFL and inner retinal thinning in patients with Alzheimer disease, which correlated with the severity of cognitive impairment. OCT studies also have demonstrated inner retina, ganglion cell complex, and RNFL thinning in patients with Parkinson disease (32–34), where the extent of thinning may correlate with the severity and duration of the disease. One article showed that there may be subclinical visual dysfunction in patients with Parkinson disease, which correlates with thinning of the ganglion cell layer (35).

OCT has been extensively used to study subjects with multiple sclerosis (MS) (36–39) and neuromyelitis optica spectrum disorder (NMOSD) (40,41). Davies et al (42) showed that patients with MS have a thinner ganglion cell complex thickness, especially if they had prior optic neuritis. Optic neuritis leads to thinning of the peripapillary RNFL in both NMOSD and MS. While NMOSD related optic neuritis tends to cause more thinning of the RNFL than MS-related optic neuritis (43,44), a study by Lange et al (41) revealed that there is an overlap between the 2 groups, and therefore RNFL alone is unable to differentiate the 2 forms of optic neuritis.

In addition, patients with MS without clinical episodes of optic neuritis have been reported to have progressive thinning of the RNFL on OCT (45,46). Abalo-Lojo et al (46) found that RNFL thickness correlated with brain atrophy and disability scores in patients with MS, and thus OCT has been proposed as a method to monitor MS disease progression. Studies on subclinical RNFL loss in NMOSD are mixed in the literature, including those published within the Journal of Neuro-Ophthalmology (43). Interestingly, a 4-year observational study of 9 patients with NMOSD without optic neuritis did not demonstrate thinning of the RNFL over time, suggesting that the lack of progressive thinning of the RNFL could be used to distinguish NMOSD from MS (47). However, a study by Brody et al (48) found that patients with NMOSD can have subclinical optic neuritis.

OCT is now an outcome measure of most clinical trials involving the optic nerve, including the idiopathic intracranial hypertension treatment trial (49–51), venous stenting for idiopathic intracranial hypertension (52), nonarteritic anterior ischemic optic neuropathy (53) and MS (37).

OCT allows for visualization of all layers of the retina and has provided insight into some disease processes. For example, 2 OCT studies showed outer plexiform layer retinal edema and subfoveal detachments in neuroretinitis, which suggests that the submacular detachments in neuroretinitis result from diffusion of fluid from the optic disc to the outer plexiform layer and through the outer limiting membrane to the subretinal space (54,55). In addition, OCT is important in documenting the ocular changes that occur during space flight, including optic disc edema and choroidal folds (56,57).

Because OCT is very sensitive in detecting optic atrophy, it has been used to detect and monitor optic neuropathies in inherited conditions. Case reports and series showed that patients with Friederich ataxia (58), spastic ataxia of Charlevoix-Saguenay (59), spinocerebellar ataxia 7 (60), and panthothenate kinase-associated neurodegeneration (61) all have RNFL thinning on OCT. One article showed central retinal thinning of the retina and disorganized photoreceptor layers on OCT in patients with spinocerebellar ataxia Type 1 (62).

While OCT is critical for the analysis of the optic nerve and retina and has revolutionized our ability to diagnose and track diseases, proper interpretation of the scans is important (63). There can be artifacts on OCT leading to misinterpretation of the imaging data. The most common artifacts of OCT were reviewed by Chen and Kardon (64). Failure to recognize these can lead to misdiagnoses or inappropriate investigations. Interestingly, an understanding of these artifacts can be used to diagnose and quantify cyclotorsion of the eyes, which was reported in a case of skew deviation from MS (65).

It is important to note that there are differences in the standard measurements obtained by the different commercially available OCT devices, including thickness of the central macula and RNFL (66). For example, eyes with no light perception from chronic optic neuropathy have been shown to have an average RNFL thickness of 45.42 μm with time-domain OCT and 34.18 μm with spectral-domain OCT (67,68). These differences are important to recognize when comparing the results from different OCT machines.

In summary, OCT is an evolving technology with faster scans and higher resolution being developed. Enhanced depth imaging and swept-source OCT allow imaging of the deeper layers of the eye. OCT angiography will allow better visualization of the capillaries and an approximation of ocular flow. These advances will ultimately provide us with a better understanding of disease pathogenesis and allow us to be better clinicians.

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